signal transduction

1. Nerve Action Potential
Sardar Changez Khan

2. Objectives
• What is action potential?
• Changes occurring during an action potential?
• Stages of action potential.
• Action potential curve
• Ionic basis of action potential Voltage gated Na+ channels and K+ channels, Ca+2 and
other negative anions.
• Types of Action Potentials Monophasic, Biphasic and Compound.
• Refractory period

3. Action Potential
• Action potential is defined as a series of electrical changes that occur in the
membrane potential when the muscle or nerve is stimulated.
• Each Action potential begins with a sudden change from normal resting
Membrane Potential and ends with an almost equally rapid change back to
negative potential.
• Changes occurring during action potential are transfer of +ve ions to inside and
–ve ions outside the membrane.

4. Stages of Action Potential

5. 1. RESTING STAGE
2. DEPOLARIZATION STAGE
3. REPOLARIZATION STAGE

6. RESTING STAGE
1. Also known as Resting Membrane Potential.
2. Membrane is said to be polarized during this stage because of -90mV (negative
MP) that is present.

7. DEPOLARIZATION STAGE
1. Membrane becomes permeable to Na+, allowing tremendous number of +vely
charged Na+ ions to diffuse to interior of axon.
2. -90mV polarized stage is immediately neutralized by inflowing +ve Na+, with
potential rising rapidly in the +ve direction.
3. In large nerve fibers, the great excess of +ve Na--. Moving to inside causes the
Membrane potential to actually overshoot, beyond zero level becoming more
+ve.
4. For smaller nerve fibers no overshoot and the potential wont cross beyond zero.

8. REPOLARIZATION STAGE
1. Within a few 10,000th of a second i.e. 0.001s approx. after membrane becomes
permeable to Na+, the Na+ channels begin to close and the K+ channels open
more than normal.
2. Rapid diffusion of K+ ions exterior
3. Re-establishment of normal –ve RMP
4. Repolarization of membrane

9. Characteristics of Action Potentials
Action potentials have three basic characteristics
1. Stereotypical size and shape
2. Propagation
3. All-or-none response.

10. 1. Stereoty pical size and shape. Each normal action potential for a given cell type looks identical,
depolarizes to the same potential, and repolarizes back to the same resting potential.
2. Propagation An action potential at one site causes depolarization at adjacent sites, bringing those
adjacent sites to threshold. Propagation of action potentials from one site to the next is
nondecremental.
3. All-or-none response An action potential either occurs or does not occur. If an excitable cell is
depolarized to threshold in a normal manner, then the occurrence of an action potential is inevitable.
On the other hand, if the membrane is not depolarized to threshold, no action potential can occur.
Indeed, if the stimulus is applied during the refractory period, then either no action potential occurs,
or the action potential will occur but not have the stereotypical size and shape.

11. ACTION POTENTIAL CURVE

12. Intro…
• The action potential curve is the graphical registration of electrical activity that
occurs in an excitable tissue such as muscle after stimulation.
• It shows three major parts
1. Latent period
2. Depolarization
3. Repolarization
• RMP in skeletal muscle is -90mV and is recorded as a straight baseline.

14. Latent Period
• Latent period is the period when no change occurs in the electrical potential
immediately after applying the stimulus. It is a very short period with duration of 0.5
to 1 millisecond.
• The latent period is a short delay (1-2 milli second) from the time when the action
potential reaches the muscle until tension can be observed in the muscle.
• When a stimulus is applied, there is a slight irregular deflection of baseline for a
very short period. This is called stimulus artifact. The artifact occurs because of the
disturbance in the muscle due to leakage of current from stimulating electrode to the
recording electrode. The stimulus artifact is followed by latent period.

15. Depolarization
• Depolarization starts after the latent period. Initially, it is very slow and the muscle is
depolarized for about 15 mV.
Firing level and depolarization
• After the initial slow depolarization for 15 mV (up to –75 mV), the rate of
depolarization increases suddenly. The point at which, the depolarization increases
suddenly is called firing level.
Overshoot
• From firing level, the curve reaches isoelectric potential (zero potential) rapidly and
then shoots up (overshoots) beyond the zero potential (isoelectric base) up to +35 mV.
It is called overshoot.

16. Repolarization
• When depolarization is completed (+35 mV), the repolarization starts. Initially, the repolarization
occurs rapidly and then it becomes slow.
Spike potential
• Rapid rise in depolarization and the rapid fall in repolarization are together called spike potential. It
lasts for 0.4 millisecond.
After depolarization
• Rapid fall in repolarization is followed by a slow repolarization. It is called after depolarization or
negative after potential. Its duration is 2 to 4 milliseconds.
After hyperpolarization
• After reaching the resting level (–90 mV), it becomes more negative beyond resting level. This is
called hyperpolarization or positive after potential. This lasts for more than 50 milliseconds. After
this, the normal resting membrane potential is restored slowly.

17. ION CHANNELS
• Ion channels are integral, membrane-spanning proteins that, when open, permit the passage of certain
ions. Thus ion channels are selective and allow ions with specific characteristics to move through
them.
• This selectivity is based on both the size of the channel and the charges lining it. For example,
channels lined with negative charges typically permit the passage of cations but exclude anions;
channels lined with positive charges permit the passage of anions but exclude cations.
• Channels also discriminate on the basis of size. For example, a cation-selective channel lined with
negative charges might permit the passage of Na+ but exclude K+ ; another cation-selective channel
(e.g., nicotinic receptor on the motor end plate) might have less selectivity and permit the passage of
several different small cations.

18. • Ion channels are controlled by gates, and, depending on the position of the
gates, the channels may be open or closed.
• When a channel is open, the ions for which it is selective can flow through it by
passive diffusion, down the existing electrochemical gradient.
• In the open state, there is a continuous path between ECF and ICF, through
which ions can flow.
• When the channel is closed, the ions cannot flow through it, no matter what the
size of the electrochemical gradient.

19. Voltage-gated channels
• Voltage-gated channels have gates that are controlled by changes in
membrane potential.
• For example, the activation gate on the nerve Na+ channel is opened by
depolarization of the nerve cell membrane; opening of this channel is
responsible for the upstroke of the action potential.
• Interestingly, another gate on the Na+ channel, an inactivation gate, is
closed by depolarization. Because the activation gate responds more rapidly
to depolarization than the inactivation gate, the Na+ channel first opens and
then closes.
• This difference in response times of the two gates accounts for the shape
and time course of the action potential.

20. Voltage gated Na+ channel
1. Two gates one near the outside of the channel called ACTIVATION
GATE another near the inside called the INACTIVATION GATE.

21. 1 2
Voltage gated K+ channel

22. • The diagram shows the voltage-gated potassium channel in two states: during the resting state (left) and toward
the end of the action potential (right).
• Resting state: the gate of the potassium channel is closed and potassium ions are prevented from passing
through this channel to the exterior.
• Activation state: When the membrane potential rises from −90 millivolts toward zero, this voltage change
causes a conformational opening of the gate and allows increased potassium diffusion outward through the
channel. However, because of the slight delay in opening of the potassium channels, for the most part, they open
just at the same time that the sodium channels are beginning to close because of inactivation.
• Thus, the decrease in sodium entry to the cell and the simultaneous increase in potassium exit from the cell
combine to speed the repolarization process, leading to full recovery of the resting membrane potential within
another few 10,000ths of a second.

24. MONOPHASIC, BIPHASIC AND COMPOUND
ACTION POTENTIALS

25. Monophasic Action Potential
Monophasic action potential is the series of electrical changes that occur in a
stimulated muscle or nerve fiber, which is recorded by placing one electrode on
its surface and the other inside. It is characterized by a positive deflection.

26. Biphasic Action Potential
• Biphasic or diphasic action potential is the series
of electrical changes in a stimulated muscle or
nerve fiber, which is recorded by placing both the
recording electrodes on the surface of the muscle
or nerve fiber.
• It is characterized by a positive deflection
followed by an isoelectric pause and a negative
deflection.

27. Compound Action Potential
• Compound action potential (CAP) is the algebraic
summation of all the action potentials produced by all
the nerve fibers.
• Each nerve is made up of thousands of axons. While
stimulating the whole nerve, all the nerve fibers are
activated and produce action potential.
• The compound action potential is obtained by recording
all the action potentials simultaneously.

28. REFRACTORY PERIODS

29. • During the refractory periods, excitable cells are incapable of producing
normal action potentials. The refractory period includes an absolute refractory
period and a relative refractory period.

30. 1. Guyton and Hall textbook of medical physiology.
2. Human physiology K. Sembulingham
REFERENCES